In the continuing international search for a mesothelioma cure, cancer researchers from multiple Japanese Universities say a bisphosphonate drug called zoledronic acid kept mesothelioma tumors from growing in mice when it was administered directly into the pleural cavity.
Novel Approach to Mesothelioma
Zoledronic acid, which is sold under the brand names Reclast and Zometa in the US, reduces high blood calcium levels by slowing the release of calcium from the bones.
It can also help prevent the breakdown of bones caused by the spread of cancer and is used to treat osteoporosis in men and postmenopausal women.
But in a report published in SpringerPlus, researchers with Chiba University, Tokyo Women’s Medical University, Toho University, and the University of Tsukuba report successfully using zoledronic acid to to improve mesothelioma survival in mice.
“We also showed that zoledronic acid produced synergistic cytotoxic effects with cisplatin, the first-line chemotherapeutic agent for mesothelioma,” writes Chiba University’s Yuji Tada, the first author on the paper.
Zoledronic Acid in Mesothelioma Therapy
There were some important differences in the way researchers used zoledronic acid to treat mesothelioma and the way it is normally used for bone diseases.
Although the drug is usually given as an intravenous injection, this delivery method had no significant impact on mesothelioma tumor growth.
Instead, mesothelioma-infected mice got an equivalent dose of zoledronic acid directly into into their pleural cavity where mesothelioma tumors grow.
Testing the Novel Mesothelioma Approach in People
Now that the research team has demonstrated in the lab and in live mice that zoledronic acid has potential as a novel mesothelioma therapy, the next step is to test the compound in people.
The team is now recruiting mesothelioma patients who have failed to respond to first-line chemotherapy for a Phase I clinical trial to establish the safety of the treatment and the most effective dose.
The dose escalation study will include five groups of patients who will all get different doses of zoledronic acid, ranging from .4 mg to 16 mg. The protocol allows for repeat dosing after 4 weeks.
Based on those results, the team plans to conduct a second study in mesothelioma patients who have never had treatment. That trial will combine the optimal zoledronic acid dose with chemotherapy to see how effectively the two agents work together.
Tada, Y, et al, “An intrapleural administration of zoledronic acid for inoperable malignant mesothelioma patients: a phase I clinical study protocol”, February 27, 2016, Springer Plus